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Cardiovascular disease is a leading cause of death worldwide, with disproportionate impacts on Indigenous Peoples in Canada. In Spring 2022, a land-based learning program was piloted and evaluated as an Indigenous cultural safety training for professionals at a cardiac care centre and university in a large urban city. Baseline and endline surveys showed an increase in knowledge of Indigenous histories, cultures, and practices; increased reflection on positionality and intention to create change; and strengthened relationships with the land. Future work should explore the long-term effects of land-based cultural safety training on participant behaviours, and health outcomes for Indigenous Peoples.

Despite the importance of osteoclast secretory lysosomes in bone digestion, the proteins that regulate them remain ill defined. Here, the authors identify Slc37a2 as a secretory lysosome sugar transporter that is required for maintenance of skeletal bone mass.

Clofazimine (CFZ) is a broad spectrum antimycobacterial agent recommended by the World Health Organization as a first line treatment for leprosy and second line treatment for multidrug resistant tuberculosis. Oral administration of CFZ leads to a red skin pigmentation side effect. Since CFZ is a weakly basic, red phenazine dye, the skin pigmentation side effect results from lipophilic partitioning of the circulating, free base (neutral) form of CFZ into the skin. Here, we developed a stable and biocompatible formulation of CFZ-HCl microcrystals that mimics the predominant form of the drug that bioaccumulates in macrophages, following long term oral CFZ administration. In mice, intravenous injection of these biomimetic CFZ-HCl microcrystals led to visible drug accumulation in macrophages of the reticuloendothelial system with minimal skin accumulation or pigmentation. In fact, no skin pigmentation was observed when the total amount of CFZ-HCl administered was equivalent to the total oral dose leading to maximal skin pigmentation. Thus, parenteral (injected or inhaled) biomimetic formulations of CFZ-HCl could be instrumental to avoid the pigmentation side effect of oral CFZ therapy.

While young muscle faithfully regenerates damaged myofibers, aged muscle is impaired. Here the authors show the “anti-aging” protein α-Klotho is upregulated in young muscle after damage via promoter demethylation and this regulation is lost in aging, resulting in mitochondrial damage and an impaired healing response.

Abstract With the capability of presenting endogenous tissue contrast or exogenous contrast agents in deep biological samples at high spatial resolution, photoacoustic (PA) imaging has shown significant potential for many preclinical and clinical applications. However, due to strong background signals from various intrinsic chromophores in biological tissue, such as hemoglobin, achieving highly sensitive PA imaging of targeting probes labeled by contrast agents has remained a challenge. In this study, we introduce a novel technique called transient triplet differential (TTD) imaging which allows for substantial reduction of tissue background signals. TTD imaging detects directly the triplet state absorption, which is a special characteristic of phosphorescence capable dyes not normally present among intrinsic chromophores of biological tissue. Thus, these triplet state absorption PA images can facilitate “true” background free molecular imaging. We prepared a known phosphorescent dye probe, methylene blue conjugated polyacrylamide nanoparticles, with peak absorption at 660 nm and peak lowest triplet state absorption at 840 nm. We find, through studies on phantoms and on an in vivo tumor model, that TTD imaging can generate a superior contrast-to-noise ratio, compared to other image enhancement techniques, through the removal of noise generated by strongly absorbing intrinsic chromophores, regardless of their identity.

Prostate cancer was the most common form and had the second highest death rate of male cancer in the United States in 2015. Current diagnosis techniques, such as prostate-specific antigen tests, transrectal ultrasound scans, and biopsies, are often inconclusive, and in the latter case, invasive. Here, we explore the use of clofazimine hydrochloride nanoparticles (CFZ-HCl NPs), a repurposed formulation from an FDA-approved antimycobacterial agent, as a photoacoustic contrast agent for the evaluation of prostate cancer due to its macrophage-targeting capabilities and high optical absorbance at 495 nm. Using a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, our results indicate a preferential accumulation of intravenously injected CFZ-HCl NPs in cancerous prostates over normal prostates. Differences in accumulation of CFZ-HCl NPs between cancerous and normal prostates were determined using a two-wavelength unmixing technique via ex vivo photoacoustic imaging. Thus, intravenous injection of CFZ-HCl NPs leads to differences in the interactions of the particles with cancerous vs normal prostates, while allowing for photoacoustic detection and analysis of prostate cancer. These findings could lead to the development of a new noninvasive technique for the detection and monitoring of prostate cancer progression in an animal model that can potentially be translated to human patients.